Criteria for optimal electrical resynchronization derived from multipolar leads or multiple electrodes during biventricular pacing

ABSTRACT

Generally, the disclosure is directed one or more methods or systems of cardiac pacing employing a right ventricular electrode and a plurality of left ventricular electrodes. Pacing using the right ventricular electrode and a first one of the left ventricular electrodes and measuring activation times at other ones of the left ventricular electrodes. Pacing using the right ventricular electrode and a second one of the ventricular electrodes and measuring activation times at other ones of the left ventricular electrodes. Employing sums of the measured activation times to select one of the left ventricular electrodes for delivery of subsequent pacing pulses.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/600,462, filed on Feb. 27, 2012. The disclosure of the aboveapplication is incorporated herein by reference in its entirety.

FIELD

The present disclosure relates to implantable medical devices (IMDs),and, more particularly, to selecting an optimal left ventricularelectrode on a medical electrical lead extending from an IMD to delivercardiac therapy delivery.

BACKGROUND

Implantable medical devices (IMD) are capable of utilizing pacingtherapies, such as cardiac resynchronization therapy (CRT), to maintainhemodynamic benefits to patients. Pacing therapy may be delivered froman implantable generator, through a lead, and into the patient's heart.There are many ways in which to optimize a pacing configuration. CRTtherapy involves biventricular pacing which consists of pacing the rightventricle (RV) with a RV electrode and a left ventricle (LV) with a LVelectrode or monoventricular pacing which consists of pacing only theleft ventricle. US Patent Publication 2011/0137639 by Ryu et al.discloses that the optimal left ventricle electrode is selected basedupon conduction velocities. Another U.S. Pat. No. 7,917,214 to Gill etal. discloses that the optimal left ventricle electrode is selectedbased upon activation times and ARI dispersions. It is desirable todevelop additional methods to optimize biventricular pacing.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of an exemplary system including anexemplary implantable medical device (IMD).

FIG. 2 is a schematic diagram of the exemplary IMD of FIG. 1.

FIG. 3-3A are schematic diagrams of an enlarged view of a distal end ofa medical electrical lead disposed in the left ventricle.

FIG. 4 is a block diagram of an exemplary IMD, e.g., the IMD of FIGS.1-2.

FIG. 5 is a general flow chart of an exemplary method that involvesdetermining a weighted electrical dyssynchrony without a baseline forselecting an optimal left ventricle electrode to pace a left ventricle.

FIG. 6A is a general flow chart of an exemplary method that involvesselecting an optimal left ventricle electrode to pace a left ventricle.

FIG. 6B is a general flow chart of another exemplary method thatinvolves selecting an optimal left ventricle electrode to pace a leftventricle.

FIG. 7 is a general flow chart of an exemplary method that involvesdetermining a weighted electrical dyssynchrony without a baseline forselecting an optimal A-V delay.

FIG. 8 is a general flow chart of an exemplary method that involvesdetermining a weighted electrical dyssynchrony without a baseline forselecting an optimal V-V delay.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

In the following detailed description of illustrative embodiments,reference is made to the accompanying figures of the drawing which forma part hereof, and in which are shown, by way of illustration, specificembodiments which may be practiced. It is to be understood that otherembodiments may be utilized and structural changes may be made withoutdeparting from (e.g., still falling within) the scope of the disclosurepresented hereby.

As described herein, a physician implanting a medical device can usecriteria, stored in a programmer, to automatically select optimizedlocation(s) and/or parameters for delivery of cardiac resynchronizationtherapy (CRT). For example, criteria can be used to determine an optimalleft ventricular electrode from which electrical stimuli is delivered tothe left ventricle. After the optimal LV electrode has been selected,other criteria can be used to optimize an atrioventricular delay, and/oran inter-ventricular delay for maximal cardiac resynchronization.Implementation of teachings of this disclosure can potentially improvecardiac resynchronization therapy (CRT) response in patients.

Exemplary methods, devices, and systems are described with reference toFIGS. 1-8. It is appreciated that elements or processes from oneembodiment may be used in combination with elements or processes of theother embodiments, and that the possible embodiments of such methods,devices, and systems using combinations of features set forth herein isnot limited to the specific embodiments shown in the Figures and/ordescribed herein. Further, it will be recognized that the embodimentsdescribed herein may include many elements that are not necessarilyshown to scale. Still further, it will be recognized that timing of theprocesses and the size and shape of various elements herein may bemodified but still fall within the scope of the present disclosure,although certain timings, one or more shapes and/or sizes, or types ofelements, may be advantageous over others.

FIG. 1 is a conceptual diagram illustrating an exemplary therapy system10 that may be used to deliver pacing therapy to a patient 14. Patient14 may, but not necessarily, be a human. The therapy system 10 mayinclude an implantable medical device 16 (IMD), which may be coupled toleads 18, 20, 22 and a programmer 24. For the sake of brevity,programmer 24 includes a computer capable of the functions representedin FIG. 4 that are incorporated herein.

The IMD 16 may be, e.g., an implantable pacemaker, cardioverter, and/ordefibrillator, that provides electrical signals to the heart 12 of thepatient 14 via electrodes coupled to one or more of the leads 18, 20,22.

The leads 18, 20, 22 extend into the heart 12 of the patient 14 to senseelectrical activity of the heart 12 and/or to deliver electricalstimulation to the heart 12. In the example shown in FIG. 1, the rightventricular (RV) lead 18 extends through one or more veins (not shown),the superior vena cava (not shown), and the right atrium 26, and intothe right ventricle 28. The left ventricular coronary sinus lead 20extends through one or more veins, the vena cava, the right atrium 26,and into the coronary sinus 30 to a region adjacent to the free wall ofthe left ventricle (LV) 32 of the heart 12. The right atrial (RA) lead22 extends through one or more veins and the vena cava, and into theright atrium 26 of the heart 12.

The IMD 16 may sense, among other things, electrical signals attendantto the depolarization and repolarization of the heart 12 via electrodescoupled to at least one of the leads 18, 20, 22. In some examples, theIMD 16 provides pacing therapy (e.g., pacing pulses) to the heart 12based on the electrical signals sensed within the heart 12. The IMD 16may be operable to adjust one or more parameters associated with thepacing therapy such as, e.g., pulse width, amplitude, voltage, burstlength, etc. Further, the IMD 16 may be operable to use variouselectrode configurations to deliver pacing therapy, which may beunipolar or bipolar. The IMD 16 may also provide defibrillation therapyand/or cardioversion therapy via electrodes located on at least one ofthe leads 18, 20, 22. Further, the IMD 16 may detect arrhythmia of theheart 12, such as fibrillation of the ventricles 28, 32, and deliverdefibrillation therapy to the heart 12 in the form of electrical pulses.In some examples, IMD 16 may be programmed to deliver a progression oftherapies, e.g., pulses with increasing energy levels, until afibrillation of heart 12 is stopped.

In some examples, a programmer 24, which may be a handheld computingdevice or a computer workstation, may be used by a user, such as aphysician, technician, another clinician, and/or patient, to communicatewith the IMD 16 (e.g., to program the IMD 16). For example, the user mayinteract with the programmer 24 to retrieve information concerning oneor more detected or indicated faults associated within the IMD 16 and/orthe pacing therapy delivered therewith. The IMD 16 and the programmer 24may communicate via wireless communication using any techniques known inthe art. Examples of communication techniques may include, e.g., lowfrequency or radiofrequency (RF) telemetry, but other techniques arealso contemplated.

FIG. 2 is a conceptual diagram illustrating the IMD 16 and the leads 18,20, 22 of therapy system 10 of FIG. 1 in more detail. The leads 18, 20,22 may be electrically coupled to a therapy delivery module (e.g., fordelivery of pacing therapy), a sensing module (e.g., one or moreelectrodes to sense or monitor electrical activity of the heart 12 foruse in determining effectiveness of pacing therapy), and/or any othermodules of the IMD 16 via a connector block 34. In some examples, theproximal ends of the leads 18, 20, 22 may include electrical contactsthat electrically couple to respective electrical contacts within theconnector block 34 of the IMD 16. In addition, in some examples, theleads 18, 20, 22 may be mechanically coupled to the connector block 34with the aid of set screws, connection pins, or another suitablemechanical coupling mechanism.

Each of the leads 18, 20, 22 includes an elongated insulative lead body,which may carry a number of conductors (e.g., concentric coiledconductors, straight conductors, etc.) separated from one another byinsulation (e.g., tubular insulative sheaths).

Exemplary leads that can be useful for the present disclosure includeU.S. Pat. Nos. 5,922,014, 5,628,778, 4,497,326, 5,443,492, 7,860,580 orUS Patent Application 20090036947 filed Apr. 30, 2008 such thatelectrodes are added and/or spaced apart in a manner similar to thatdisclosed in the figures of the present application, all of listedpatents and applications are incorporated by reference in theirentirety. Additional lead and electrode configurations that may beadapted for use with the present disclosure by adjust ing lead shape,length, electrode number and/or electrode to effectively avoid phrenicnerve stimulation as described herein are generally disclosed in U.S.Pat. Nos. 7,031,777, 6,968,237, and US Publication No. 2009/0270729, allof which are incorporated herein by reference in their entirety.Moreover, U.S. Pat. No. 7,313,444, incorporated by reference, disclosesa LV pacing lead such that the LV electrodes are about equally spaced,which could also be used to implement the present disclosure.

In the illustrated example, bipolar or unipolar electrodes 40, 42 (alsoreferred to as RV electrodes) are located proximate to a distal end ofthe lead 18. Referring briefly to FIGS. 3-3A, the electrodes 44, 45, 46are located proximate to a distal end of the lead 20 and the bipolar orunipolar electrodes 56, 50 (FIG. 2) are located proximate to a distalend of the lead 22. Electrodes 44, 45, 46 and 47 can be bipolarelectrodes, unipolar electrodes or a combination of bipolar and unipolarelectrodes. Additionally, electrodes 44, 45, 46 and 47 have an electrodesurface area of about 5.3 mm² to about 5.8 mm². Electrodes 44, 45, 46,and 47 are also referred to as LV1 (electrode 1), LV2 (electrode 2), LV3(electrode 3), and LV4 (electrode 4), respectively. As shown, lead 20includes a proximal end 92 and a distal end 94. The distal end 94 isplaced in or near LV tissue. Skilled artisans appreciate that LVelectrodes (i.e. left ventricle electrode 1 (LV1) 44, left ventricleelectrode 2 (LV2) 45, left ventricle electrode 3 (LV3) 46, and leftventricle 4 (LV4) 47 etc.) on lead 20 can be spaced apart at variabledistances. For example, electrode 44 is a distance 96 a (e.g. about 21mm) away from electrode 45, electrodes 45 and 46 are spaced a distance96 b (e.g. about 1.3 mm to about 1.5 mm) away from each other, andelectrodes 46 and 47 are spaced a distance 96 c (e.g. 20 mm to about 21mm) away from each other.

The electrodes 40, 44, 45, 46, 47, 48 may take the form of ringelectrodes, and the electrodes 42, 47, 50 may take the form ofextendable helix tip electrodes mounted retractably within theinsulative electrode heads 52, 54, 56, respectively. Each of theelectrodes 40, 42, 44, 45, 46, 47, 48, 50 may be electrically coupled toa respective one of the conductors (e.g., coiled and/or straight) withinthe lead body of its associated lead 18, 20, 22, and thereby coupled torespective ones of the electrical contacts on the proximal end of theleads 18, 20, 22. The electrodes 40, 42, 44, 45, 46, 47, 48, 50 mayfurther be used to sense electrical signals attendant to thedepolarization and repolarization of the heart 12. The electricalsignals are conducted to the IMD 16 via the respective leads 18, 20, 22.In some examples, the IMD 16 may also deliver pacing pulses via theelectrodes 40, 42, 44, 45, 46, 47, 48, 50 to cause depolarization ofcardiac tissue of the patient's heart 12. In some examples, asillustrated in FIG. 2, the IMD 16 includes one or more housingelectrodes, such as housing electrode 58, which may be formed integrallywith an outer surface of a housing 60 (e.g., hermetically-sealedhousing) of the IMD 16 or otherwise coupled to the housing 60. Any ofthe electrodes 40, 42, 44, 45, 46, 47, 48 and 50 may be used forunipolar sensing or pacing in combination with housing electrode 58.Further, any of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, which arenot being used to deliver pacing therapy, may be used to senseelectrical activity during pacing therapy (e.g., for use in determiningelectrical activation times). Electrical activation time can be used todetermine whether pacing (e.g. LV only pacing or biventricular pacing)produces effective contraction of the heart based on metrics ofelectrical dyssynchrony derived from the ventricular activation times.

Electrical activation time or local electrical activity is determinedrelative to timing of a fiducial, an indicator of a global cardiac event(e.g. timing of contraction of a chamber of the heart, timing of pacingof a chamber of the heart, etc.) For example, the fiducial may be theonset of QRS, the peak of QRS (e.g. minimum values, minimum slopes,maximum slopes), zero crossings, threshold crossings, etc. of a near orfar-field EGM), onset of application of a pacing electrical stimulus, orthe like. After a fiducial point is selected, activation times aredetermined by measuring time between the delivery of pacing stimulususing a pacing electrode and the appropriate fiducial point with theelectrical activity sensed by a non-pacing electrode. The timing may bethe initiation of the pacing signal or the like. The device deliveringthe pacing signal may include appropriate electronics to track and markthe timing of the pacing signal, which marked or tracked time may beused for purposes of determining local activation time and electricaldispersion as discussed above. The device that delivers the pacingsignal may be a device configured for delivering CRT.

As described in further detail with reference to FIG. 4, the housing 60may enclose a therapy delivery module that may include a stimulationgenerator for generating cardiac pacing pulses and defibrillation orcardioversion shocks, as well as a sensing module for monitoring thepatient's heart rhythm. Cardiac pacing involves delivering electricalpacing pulses to the patient's heart, e.g., to maintain the patient'sheart beat (e.g., to regulate a patient's heart beat, to improve and/ormaintain a patient's hemodynamic efficiency, etc.). Cardiac pacinginvolves delivering electrical pacing pulses ranging from about 0.25volts to about 8 volts and more preferably, between 2-3 volts.

The leads 18, 20, 22 may also include elongated electrodes 62, 64, 66,respectively, which may take the form of a coil. The IMD 16 may deliverdefibrillation shocks to the heart 12 via any combination of theelongated electrodes 62, 64, 66 and the housing electrode 58. Theelectrodes 58, 62, 64, 66 may also be used to deliver cardioversionpulses to the heart 12. Further, the electrodes 62, 64, 66 may befabricated from any suitable electrically conductive material, such as,but not limited to, platinum, platinum alloy, and/or other materialsknown to be usable in implantable defibrillation electrodes. Sinceelectrodes 62, 64, 66 are not generally configured to deliver pacingtherapy, any of electrodes 62, 64, 66 may be used to sense electricalactivity during pacing therapy (e.g., for use in determining activationtimes). In at least one embodiment, the LV elongated electrode 64 may beused to sense electrical activity of a patient's heart during thedelivery of pacing therapy. Electrodes used to sense a response fromcardiac tissue are transmitted to an ND converter to convert the analogsignal to a digital signal. The digital signal is then transmitted tothe microprocessor 80. The microprocessor 80 determines the level ofresponse sensed at a particular electrode.

The configuration of the exemplary therapy system 10 illustrated inFIGS. 1-2 is merely one example. In other examples, the therapy systemmay include epicardial leads and/or patch electrodes instead of or inaddition to the transvenous leads 18, 20, 22 illustrated in FIG. 1.Further, in one or more embodiments, the IMD 16 need not be implantedwithin the patient 14. For example, the IMD 16 may deliverdefibrillation shocks and other therapies to the heart 12 viapercutaneous leads that extend through the skin of the patient 14 to avariety of positions within or outside of the heart 12. In one or moreembodiments, the system 10 may utilize wireless pacing (e.g., usingenergy transmission to the intracardiac pacing component(s) viaultrasound, inductive coupling, RF, etc.) and sensing cardiac activationusing electrodes on the can/housing and/or on subcutaneous leads.

In other examples of therapy systems that provide electrical stimulationtherapy to the heart 12, such therapy systems may include any suitablenumber of leads coupled to the IMD 16, and each of the leads may extendto any location within or proximate to the heart 12. Other examples oftherapy systems may include three transvenous leads located asillustrated in FIGS. 1-3. Still further, other therapy systems mayinclude a single lead that extends from the IMD 16 into the right atrium26 or the right ventricle 28, or two leads that extend into a respectiveone of the right atrium 26 and the right ventricle 28.

FIG. 4 is a functional block diagram of one exemplary configuration ofthe IMD 16. As shown, the IMD 16 may include a control module 81, atherapy delivery module 84 (e.g., which may include a stimulationgenerator), a sensing module 86, and a power source 90.

The control module 81 may include a processor 80, memory 82, and atelemetry module 88. The memory 82 may include computer-readableinstructions that, when executed, e.g., by the processor 80, cause theIMD 16 and/or the control module 81 to perform various functionsattributed to the IMD 16 and/or the control module 81 described herein.Further, the memory 82 may include any volatile, non-volatile, magnetic,optical, and/or electrical media, such as a random access memory (RAM),read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasableprogrammable ROM (EEPROM), flash memory, and/or any other digital media.

The processor 80 of the control module 81 may include any one or more ofa microprocessor, a controller, a digital signal processor (DSP), anapplication specific integrated circuit (ASIC), a field-programmablegate array (FPGA), and/or equivalent discrete or integrated logiccircuitry. In some examples, the processor 80 may include multiplecomponents, such as any combination of one or more microprocessors, oneor more controllers, one or more DSPs, one or more ASICs, and/or one ormore FPGAs, as well as other discrete or integrated logic circuitry. Thefunctions attributed to the processor 80 herein may be embodied assoftware, firmware, hardware, or any combination thereof.

The control module 81 may control the therapy delivery module 84 todeliver therapy (e.g., electrical stimulation therapy such as pacing) tothe heart 12 according to a selected one or more therapy programs, whichmay be stored in the memory 82. More, specifically, the control module81 (e.g., the processor 80) may control the therapy delivery module 84to deliver electrical stimulus such as, e.g., pacing pulses with theamplitudes, pulse widths, frequency, or electrode polarities specifiedby the selected one or more therapy programs (e.g., pacing therapyprograms, pacing recovery programs, capture management programs, etc.).As shown, the therapy delivery module 84 is electrically coupled toelectrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66, e.g., viaconductors of the respective lead 18, 20, 22, or, in the case of housingelectrode 58, via an electrical conductor disposed within housing 60 ofIMD 16. Therapy delivery module 84 may be configured to generate anddeliver electrical stimulation therapy such as pacing therapy to theheart 12 using one or more of the electrodes 40, 42, 44, 45, 46, 47, 48,50, 58, 62, 64, 66.

For example, therapy delivery module 84 may deliver pacing stimulus(e.g., pacing pulses) via ring electrodes 40, 44, 48 coupled to leads18, 20, and 22, respectively, and/or helical tip electrodes 42, 46, and50 of leads 18, 20, and 22, respectively. Further, for example, therapydelivery module 84 may deliver defibrillation shocks to heart 12 via atleast two of electrodes 58, 62, 64, 66. In some examples, therapydelivery module 84 may be configured to deliver pacing, cardioversion,or defibrillation stimulation in the form of electrical pulses. In otherexamples, therapy delivery module 84 may be configured deliver one ormore of these types of stimulation in the form of other signals, such assine waves, square waves, and/or other substantially continuous timesignals.

The IMD 16 may further include a switch module 85 and the control module81 (e.g., the processor 80) may use the switch module 85 to select,e.g., via a data/address bus, which of the available electrodes are usedto deliver therapy such as pacing pulses for pacing therapy, or which ofthe available electrodes are used for sensing. The switch module 85 mayinclude a switch array, switch matrix, multiplexer, or any other type ofswitching device suitable to selectively couple the sensing module 86and/or the therapy delivery module 84 to one or more selectedelectrodes. More specifically, the therapy delivery module 84 mayinclude a plurality of pacing output circuits. Each pacing outputcircuit of the plurality of pacing output circuits may be selectivelycoupled, e.g., using the switch module 85, to one or more of theelectrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 (e.g., a pairof electrodes for delivery of therapy to a pacing vector). In otherwords, each electrode can be selectively coupled to one of the pacingoutput circuits of the therapy delivery module using the switchingmodule 85.

The sensing module 86 is coupled (e.g., electrically coupled) to sensingapparatus, which may include, among additional sensing apparatus, theelectrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 to monitorelectrical activity of the heart 12, e.g., electrocardiogram(ECG)/electrogram (EGM) signals, etc. The ECG/EGM signals may be used tomonitor heart rate (HR), heart rate variability (HRV), heart rateturbulence (HRT), deceleration/acceleration capacity, decelerationsequence incidence, T-wave alternans (TWA), P-wave to P-wave intervals(also referred to as the P-P intervals or A-A intervals), R-wave toR-wave intervals (also referred to as the R-R intervals or V-Vintervals), P-wave to QRS complex intervals (also referred to as the P-Rintervals, A-V intervals, or P-Q intervals), QRS-complex morphology, STsegment (i.e., the segment that connects the QRS complex and theT-wave), T-wave changes, QT intervals, electrical vectors, etc.

The switch module 85 may also be used with the sensing module 86 toselect which of the available electrodes are used, e.g. to senseelectrical activity of the patient's heart. In some examples, thecontrol module 81 may select the electrodes that function as sensingelectrodes via the switch module within the sensing module 86, e.g., byproviding signals via a data/address bus. In some examples, the sensingmodule 86 may include one or more sensing channels, each of which mayinclude an amplifier.

In some examples, sensing module 86 includes a channel that includes anamplifier with a relatively wider pass band than the R-wave or P-waveamplifiers. Signals from the selected sensing electrodes that areselected for coupling to this wide-band amplifier may be provided to amultiplexer, and thereafter converted to multi-bit digital signals by ananalog-to-digital converter (ND) for storage in memory 82 as anelectrogram (EGM). In some examples, the storage of such EGMs in memory82 may be under the control of a direct memory access circuit. Thecontrol module 81 (e.g., using the processor 80) may employ digitalsignal analysis techniques to characterize the digitized signals storedin memory 82 to detect and classify the patient's heart rhythm from theelectrical signals. For example, the processor 80 may be configured tomeasure activation times of cardiac tissue using EGMs from one or moreelectrodes in contact, or in proximity, with cardiac tissue by employingany of the numerous signal processing methodologies known in the art.

If IMD 16 is configured to generate and deliver pacing pulses to theheart 12, the control module 81 may include a pacer timing and controlmodule, which may be embodied as hardware, firmware, software, or anycombination thereof. The pacer timing and control module may include oneor more dedicated hardware circuits, such as an ASIC, separate from theprocessor 80, such as a microprocessor, and/or a software moduleexecuted by a component of processor 80, which may be a microprocessoror ASIC. The pacer timing and control module may include programmablecounters which control the basic time intervals associated with DDD, WI,DVI, VDD, AAI, DDI, DDDR, VVIR, DVIR, VDDR, AAIR, DDIR and other modesof single and dual chamber pacing. In the aforementioned pacing modes,“D” may indicate dual chamber, “V” may indicate a ventricle, “I” mayindicate inhibited pacing (e.g., no pacing), and “A” may indicate anatrium. The first letter in the pacing mode may indicate the chamberthat is paced, the second letter may indicate the chamber in which anelectrical signal is sensed, and the third letter may indicate thechamber in which the response to sensing is provided.

Intervals defined by the pacer timing and control module within controlmodule 81 may include atrial and ventricular pacing escape intervals,refractory periods during which sensed P-waves and R-waves areineffective to restart timing of the escape intervals, and/or the pulsewidths of the pacing pulses. As another example, the pacer timing andcontrol module may define a blanking period, and provide signals fromsensing module 86 to blank one or more channels, e.g., amplifiers, for aperiod during and after delivery of electrical stimulation to the heart12. The durations of these intervals may be determined in response tostored data in memory 82. The pacer timing and control module of thecontrol module 81 may also determine the amplitude of the cardiac pacingpulses.

During pacing, escape interval counters within the pacer timing/controlmodule may be reset upon sensing of R-waves and P-waves. Therapydelivery module 84 (e.g., including a stimulation generator) may includeone or more pacing output circuits that are coupled, e.g., selectivelyby the switch module 85, to any combination of electrodes 40, 42, 44,45, 46, 47, 48, 50, 58, 62, or 66 appropriate for delivery of a bipolaror unipolar pacing pulse to one of the chambers of heart 12. The controlmodule 81 may reset the escape interval counters upon the generation ofpacing pulses by therapy delivery module 84, and thereby control thebasic timing of cardiac pacing functions, including anti-tachyarrhythmiapacing.

In some examples, the control module 81 may operate as an interruptdriven device, and may be responsive to interrupts from pacer timing andcontrol module, where the interrupts may correspond to the occurrencesof sensed P-waves and R-waves and the generation of cardiac pacingpulses. Any necessary mathematical calculations may be performed by theprocessor 80 and any updating of the values or intervals controlled bythe pacer timing and control module may take place following suchinterrupts. A portion of memory 82 may be configured as a plurality ofrecirculating buffers, capable of holding series of measured intervals,which may be analyzed by, e.g., the processor 80 in response to theoccurrence of a pace or sense interrupt to determine whether thepatient's heart 12 is presently exhibiting atrial or ventriculartachyarrhythmia.

The telemetry module 88 of the control module 81 may include anysuitable hardware, firmware, software, or any combination thereof forcommunicating with another device, such as the programmer 24 asdescribed herein with respect to FIG. 1. For example, under the controlof the processor 80, the telemetry module 88 may receive downlinktelemetry from and send uplink telemetry to the programmer 24 with theaid of an antenna, which may be internal and/or external. The processor80 may provide the data to be uplinked to the programmer 24 and thecontrol signals for the telemetry circuit within the telemetry module88, e.g., via an address/data bus. In some examples, the telemetrymodule 88 may provide received data to the processor 80 via amultiplexer. In at least one embodiment, the telemetry module 88 may beconfigured to transmit an alarm, or alert, if the pacing therapy becomesineffective or less effective.

The various components of the IMD 16 are further coupled to a powersource 90, which may include a rechargeable or non-rechargeable battery.A non-rechargeable battery may be selected to last for several years,while a rechargeable battery may be inductively charged from an externaldevice, e.g., on a daily or weekly basis.

After the LV lead 20 has been properly positioned on or near the LVtissue, schematically shown in FIG. 3, a variety of pacingconfigurations (e.g. biventricular pacing configurations, LV only pacingetc.) can be tested. Data generated from each pacing configuration canbe useful in determining the optimal LV electrode from which to pace theLV. Biventricular pacing configurations are defined by a RV electrodepacing the RV while one or more LV electrodes pace the LV. Eachbiventricular configuration employs a different LV electrode (e.g. LV1,LV2, LV3, and LV4 etc.) for pacing.

Exemplary methods and/or devices described herein evaluate theeffectiveness of pacing based on metrics of electrical dyssynchronyderived from the measured cardiac electrical activation times for eachbiventricular pacing configuration employing a different LV electrode.FIGS. 5-8 flow diagrams present different exemplary methods forselecting an optimal LV electrode.

Exemplary method 100, depicted in FIG. 5, evaluates differentbiventricular pacing configurations in order to determine which LVelectrode on lead 20 is optimal for pacing the LV. Each of the availablebiventricular pacing configurations is serially tested and evaluated byprogrammer 24 as to its effectiveness based on the metrics of electricaldyssynchrony. The optimal biventricular pacing configuration is selectedbased on one or more of these metrics.

At block 102, the programmer 24 switches the RV electrode 42 and one ofthe LV electrodes 44, 45, 46, 47 to a pacing mode while the other LVelectrodes remain in the sensing mode. The LV electrode that is selectedfor pacing the LV is designated as the j-th LV electrode. The first LVelectrode out of the plurality of LV electrodes to pace the LV isreferred to in the claims as the first LV electrode. The programmer 24includes a pulse generator that generates pacing pulses (e.g. 2-3 voltsamplitude) that are delivered through the pacing LV electrode to the LVwhile other pacing pulses (e.g. 2-3 volts amplitude) are transmittedthrough the RV electrode to the RV. The non-pacing LV electrodes sensefrom the LV tissue the electrical response such as the activation times.The sensed signals are transmitted to an A/D converter that converts theanalog signals to digital signals. Digital signals are then transmittedto the microprocessor 80 so that sensed signals can be measured and thenstored into memory 82 at operation 104.

At block 106, after obtaining the electrical activation times (e.g.determined with respect to the timing of the earliest ventricular pacingor any other suitable means) at non-pacing electrodes, themicroprocessor 80 determines the weighted electrical dyssynchrony indexfor the first biventricular pacing configuration. Electrical dyssynchonyor cardiac dyssynchrony involves improperly timed electrical activationof one or more different parts of the heart.

An electrical dyssynchrony index (ED) of LV electrical dyssynchrony[ED(j, A, D)] can be computed for each pacing electrode j from a linearcombination of electrical activation times (AT(i, A, D)) at each sensingLV electrode denoted by i. “A” of ED(j, A, D) refers to theatrio-ventricular delay between atrial sense (pace) and the firstventricular pacing pulse, and “D” refers to the time delay between thepacing pulses in the RV and the LV. A determination of ED for each LVelectrode may be made initially at a nominal values of A and D. Anominal value of “A” may be 50 ms, the nominal value of D can be about 0ms, which is simultaneous biventricular pacing.

ED is determined by a weighted linear combination of electricalactivation times in which individual weights are determined dependingupon the lead-geometry and the inter-electrode spacing on the lead. Inparticular, ED is weighted by a suitable factor w(i, j) that is based onthe distance of the sensing electrode (designated “i”, from the pacingelectrode (designated “j”). Accordingly, the equation for calculating aweighted ED is as follows:ED(j,A,D)=Σ_(i=1) ^(n) w(i,j)AT(i,A,D)“n” is the total number of LV electrodes.

Only valid ED are used to determine an optimal LV electrode from whichto pace. A valid ED typically occurs over multiple beats (e.g. 5 beatsetc.) during pacing from a selected LV electrode to ensure thatmeasurements are consistent and repeatable. Additionally, automatic LVand RV capture detection is turned on to ensure that pacing pulsedelivered in each ventricle captures. ED is not computed for instanceswhere RV or LV or both RV and LV do not capture. Capture detection canbe verified by determining the amplitude of an evoked response at thepacing electrode. For example, an amplitude greater than 0.5 mV may beindicative of capture. Variability of ED values should be less than acertain predetermined value such as 5 ms. Additionally, valid EDrequires AT(i, A, D)>0 for all i where i designates the LV electrodenumber. Negative values for one or more AT(i) are omitted. A negativevalue of AT(i, A,D) may be caused by anomalous ventricular activationsuch as a premature beat. If |AT(i+1, A, D)−AT(i, A, D)|>50 ms, thenslow electrical conduction can exist or a block, attributable to infarctor functional block, can be identified between electrodes i and i+1.

ED is typically computed with interventricular (V-V) delay (D) valueand/or the atrioventricular delay (A) set at a constant value whenevaluating each LV electrode. For example, the A-V delay can be set at apreselected value (e.g. 0 to about 50 ms etc.) while the V-V delay canalso be preselected (e.g. 0 to 55 ms) for each biventricular pacingconfiguration such as LV1+RV, LV2+RV, LV3+RV, LV4+RV . . . LVN+RV whereN is the total number of electrodes. Assume A=50 ms and D=0 (i.e.simultaneous biventricular pacing) while evaluating each of the LVelectrodes or with a V-V delay as is discussed in greater detail below.Additionally, skilled artisans appreciate that the activation time forthe pacing electrode which captures the tissue may be 0 or may beskipped.

After an ED has been determined for the first LV electrode, theprogrammer 24 automatically selects, a second biventricular pacingconfiguration in which a second LV electrode paces the LV while the RVelectrode paces the RV at operation 108. The first LV electrode isswitched to the sensing mode. The programmer 24 causes the pulsegenerator to generate pacing pulses (e.g. 2-3 volts amplitude) that aredelivered through the second LV electrode to the LV while other pacingpulses (e.g. 2-3 volts amplitude) are transmitted through the RVelectrode to the RV. The non-pacing LV electrodes sense the electricalresponse (e.g. activation time data etc.) from the LV tissue. The sensedsignals are transmitted to an A/D converter that converts the analogsignals to digital signals. Digital signals are then transmitted to themicroprocessor 80 so that sensed signals can be measured and then storedinto memory 82 at operation 110. After obtaining the electricalactivation times at non-pacing electrodes, the microprocessor 80determines a weighted electrical dyssynchrony index associated with thesecond LV pacing electrode at operation 112. Skilled artisans appreciatethat blocks 108-112 are repeated for all of the remaining LV electrodes(e.g. LV3, LV4 etc.) at the distal end of lead 20.

Once two or more valid EDs have been calculated, electrode eliminationrules can be applied to the EDs to eliminate LV electrodes in order todetermine the optimal LV electrode at operation 114. The ED for eachelectrode can be determined for the set of electrodes before applicationof the set of rules. Alternatively, the rules can be applied afterdetermining an ED for any two electrodes and once one of the twoelectrodes is eliminated, an ED is calculated for yet another electrodeto be compared to the ED of the remaining electrode.

Examples of the manner in which ED are calculated are presented below asto the set of LV electrodes (i.e. left ventricle electrode 1 (LV1) 44,left ventricle electrode 2 (LV2) 45, left ventricle electrode 3 (LV3)46, and left ventricle 4 (LV4) 47 etc.) shown on the LV medicalelectrical lead 20; however, it is appreciated that teachings presentedherein can be applied to two or more LV electrodes on a medicalelectrical lead.

While pacing from LV1 during simultaneous biventricular pacing (D=0) andA=50 ms, the ED is computed below. For these nominal values of A and D,the ED for the biventricular pacing with the j-th LV electrode and theactivation time at the i-th LV electrode during such biventricularpacing are represented by ED(j) and AT(i) respectively. The weighted EDfor pacing at LV1 can be rewritten as follows:ED(1)=AT(1)+AT(2,3)+AT(4)/2 where AT(2,3)=[AT(2)+AT(3)]/2

Since LV2 and LV3 are substantially close, the AT of LV2 and LV3 areaveraged together. The AT associated with LV4 is muliplied by a constantnumber w(i, j). W(i, j) is a weighting factor that depends on thedistance from LV1 to LV4 as compared to the distance between LVelectrodes (2,3) and LV1. In this example, w(4,1) is ½ since thedistance from LV1 to LV4 is twice as long as the distance fromelectrodes (2,3) to LV1. W(i, j) can be adjusted depending upon the LVmedical electrical lead and the spacing used between the plurality ofelectrodes thereon.

Evaluation of ED and activation propagation is also performed whilepacing from other LV electrodes 2, 3 and 4 in the quadripolar lead 20during simultaneous biventricular pacing. The equation for calculatingweighted ED at LV2 or LV3 is as follows:ED(2)=AT(1)+AT(2,3)+AT(4)ED(3)=AT(1)+AT(2,3)+AT(4) where AT(2,3)=[AT(2)+AT(3)]/2Since the spacing between LV2 and LV3 is less than 2 mm, and LV1 and LV4are about equidistant from LV2 and LV3, the activation times areweighted equally while computing ED for LV2 and LV3.

The equation for calculating a weighted ED at LV4 is as follows:ED(4)=AT(1)/2+AT(2,3)+AT(4) where AT(2,3)=[AT(2)+AT(3)]/2After weighted ED calculations are performed, the optimal LV electrodeis selected at block 114.

FIG. 6A shows a method 200 in which the optimal LV electrode is selectedfrom the plurality LV electrodes (e.g. LV1, LV2, LV3, and LV4) through aprocess of electrode elimination. The process of elimination employs twodifferent types of electrode comparisons that are used to eliminate anelectrode from each pair of electrodes until the sole remainingelectrode is deemed to be the optimal LV electrode. The process ofeliminating an electrode begins at block 202 in which activation timesare measured at the LV electrodes (e.g. LV1, LV2, LV3, and LV4) duringbaseline rhythm which may constitute RV only pacing or intrinsic rhythm.RV only pacing occurs when the pulse generator from the programmer 24delivers electrical stimulation (i.e. pacing pulses) through an RVelectrode to the RV and none of the LV electrodes are used to pace theLV. Sensing the activation times at all of the LV electrodes (e.g. LV1,LV2, LV3, and LV4) during RV only pacing or during intrinsic rhythm canbe performed any time after LV lead 20 has been placed near and/or on LVtissue. For example, RV only pacing can occur before or after any of thebiventricular pacing configurations are tested.

At block 204, the activation times associated with each of the LVelectrodes are stored into the memory 82. At block 206, variablesthreshold (T) level, integer (I), and total number of electrodes (N)(e.g. N=4 on the distal end of lead 20) are initialized, set, and storedinto memory 82. Threshold T can be predetermined and input into theprogrammer 24 by the user before evaluating each LV electrode (e.g. LV1,LV2, LV3, LV4). Preferably, T equals 15 ms or less. A value of T equalto 15 ms or less can be typical of a left bundle branch block (LBBB)patient with a QRS of 150 ms. Additionally, T equal to 15 ms or less istypically about a 10% time of total ventricular activation. In one ormore other embodiments, T equals 10 ms or less.

I and N are used in a counting loop (i.e. blocks 206, 230 and 232) thatensures that data for each LV electrode (e.g. LV1, LV2, LV3, and LV4)are analyzed before the optimal LV electrode is selected. I=1 since EDis determined for only one LV electrode at block 208 by processor 80 andstored in memory 82. The data for determining the ED for one LVelectrode can be selected from any one of the LV electrodes (e.g. LV1,LV2, LV3, and LV4). At block 210, data for another LV electrode isretrieved from memory 82 by processor 80. Determining the ED for anotherLV electrode means any other LV electrode data not previously analyzed.For example, if the ED for one LV electrode at block 208 is data relatedto LV1, then data for another LV electrode can be related to LV2, LV3,or LV4. For the sake of illustration, assume that the data for anotherLV electrode is associated with LV2. Therefore, the ED for LV2 iscalculated by processor 80 and stored in memory 82.

At block 212, the difference in magnitude between one ED data andanother ED data is determined. For example, the ED data for oneelectrode (i.e. LV2) is subtracted from ED data for another electrode(i.e. LV1). At block 214, the difference between one ED data (i.e. ED1)and another ED data (i.e. ED2) is compared to a threshold level T (alsoreferred to as delta T or AT). At block 216, if the difference is notless than T, then the NO path can be followed to block 218. At operation218, whichever electrode is associated with a larger ED is automaticallyeliminated from consideration as a potential optimal LV electrodeirrespective of the eliminated electrode's activation time obtainedduring intrinsic rhythm or RV only pacing.

The counting loop increases the variable I by one at block 230. At block232, a determination is made as to whether I=N. Since after the firstpass of the counting loop I=2 and N=4, the NO path transfers control toblock 210 to retrieve ED data for yet another LV electrode. ED is thencalculated for yet another LV electrode (e.g. LV3) and then stored intomemory 82. Skilled artisans appreciate that after an electrode iseliminated, at either block 218 or 228, and ED data for anotherelectrode is retrieved, a swapping operation may be performed. Forexample, if data for LV2 is initially designated as “another LVelectrode” and LV2 is eliminated, then data for LV3 is swapped for theED data for LV2 and the ED data for LV3 is now stored in the registerfor “another ED data” at block 210. The electrode pair comparisons arethen between LV1 and LV3 and so on.

Returning to block 216, if the difference in ED value is less than T,the YES path transfers control to block 222. At block 222, the baseline(intrinsic rhythm or RV only pacing) AT data for one electrode (i.e.LV1) is compared to the baseline AT data for another electrode (i.e.LV3). The baseline AT data is preferably obtained during intrinsicrhythm or RV only pacing. Comparing one baseline AT to another baselineAT can involve a sorting function that places the data in ascendingorder or descending order. At block 224, a determination is made as towhether one baseline AT is less than another baseline AT. If onebaseline AT is less than another baseline AT, the YES path can befollowed to block 226.

Returning to block 223, if one baseline AT is equal to the otherbaseline AT, then both electrodes are retained in a preference list. Atblock 225, one of the two electrodes can be eliminated based uponadditional or other criteria such as lower capture threshold, higherimpedance (i.e., reduced energy required to pace), or absence of phrenicstimulation could be considered (by the user) to select the bestelectrode of two electrodes that have equivalent ATs.

At block 226, one electrode (i.e. LV1) is eliminated. I is incrementedby 1 at block 230. At block 232, a determination is made as to whetherI=N, which essentially determines whether ED data has yet to beretrieved.

Returning to block 224, if one baseline AT is not less than anotherbaseline AT, the NO path can be followed to block 228 in which anotherelectrode (i.e. LV2) is eliminated. The counting loop at block 232 isthen used to determine whether any additional ED data must be processed.At block 232, once I=N, no additional ED data needs to be processed.Therefore, the YES path can be followed to block 234. The optimalelectrode is then designated as the LV electrode that remains or has notbeen eliminated. The optimal LV electrode is set to pace the LVautomatically by programmer 24 or manually by the user.

Examples, presented below, show the electrode elimination process usedto select an optimal LV electrode. In these examples, assumptions aremade. For blocks 222, and 224, activation times for the LV electrodesare performed during RV only pacing or during intrinsic rhythm. Incontrast, the ED data was generated using the biventricular pacingconfigurations, as previously described herein. Additionally, aquadripolar LV lead 20 is used that includes four LV electrodes, LV1,LV2, LV3, and LV4; however, skilled artisans appreciate that otherembodiments could use two or more LV electrodes on a lead 20 such as twoor more electrodes on one lead and two or more electrodes on anotherlead. Each example will be described relative to FIG. 6A.

In the first example, assume that the order of activation times duringRV only pacing or intrinsic rhythm is AT(LV4)>AT(LV1)>AT(LV2)>AT(LV3)with LV4 being the latest activation time and LV3 being the earliestactivation time. Assume also that the values of ED, determined from thebiventricular configurations previously discussed are as follows:ED(1)=50 ms, ED(2)=55 ms, ED(3)=58 ms, and ED(4)=74 ms. Otherassumptions include that D=0, A is a constant (e.g., 50 ms), and that apredetermined threshold T of 15 ms is used to analyze the ED data.Processor 80 retrieves ED data such as ED(1) and ED(2) at blocks 208,210, respectively.

At block 212, the difference in magnitude between ED(1) and ED(2) iscalculated as follows:ED(2)−ED(1)=55 ms−50 ms=5 ms

At block 214, the difference in ED(1) and ED(2) is compared to thethreshold T. At block 216, a determination is made as to whether thedifference in ED(1) and ED(2) is less than the predetermined thresholdof 15 ms. Since the difference (i.e. 5 ms) in ED(1) and ED(2) is lessthan T, the YES path is followed to block 222 in which the AT values(i.e. AT(1), AT(2)) are compared. In one or more embodiments, thecompare function can also include sorting the activation times inascending order or descending order.

At block 223, if one baseline AT is equal to the other baseline AT, thenboth electrodes are retained in a preference list. One of the twoelectrodes is eliminated based upon the previously described criteria atblock 225. If one AT does not equal another AT, the NO path goes toblock 224.

At block 224, a determination is made as to whether one AT (i.e. AT1) isless than another AT (i.e. AT2). As is known from the given facts, theactivation time for one AT (i.e. AT1) is greater than another AT (i.e.AT2). The NO path can be followed to block 228, which causes theelimination of another electrode (i.e. LV2). The variable I is increasedby 1 at block 230. At block 232, a determination is made as to whetherI=N. Since I=2 and N=4, I does not equal N. The NO path returns to block210 for processor 80 to retrieve from memory 82 another ED value foranother LV electrode (e.g. LV3).

The ED value of LV3 is then subtracted from the ED value for LV1 atblock 212.ED(3)−ED(1)=58 ms-50 ms=8 ms

The difference in magnitude (i.e. 8 ms) between ED(1) and ED(3) is lessthan the predetermined threshold of 15 ms at block 216. The YES path canbe followed to block 222. At block 222, the activation times betweenAT(1) and AT(3) are compared to each other. As previously stated, AT(1)is greater than AT(3). LV3 is then eliminated based on its earlieractivation time compared to LV1 at block 228.

At block 230, the variable I is again increased by 1 which causes I=3. Adetermination is made as to whether I=N at block 232. Since I does notequal N, the NO path is followed to block 210. The ED data for the nextelectrode, ED(4), is then then retrieved at block 210.

ED(1) data, associated with LV1, is subtracted from ED(4) at block 212.At block 214, the difference in ED values is 24 ms, which is greaterthan the pre-determined threshold of 15 ms. The NO path can be followedto block 218 in which the electrode to be eliminated is associated withthe larger ED data. The electrode with the larger ED, i.e. LV4, iseliminated without any comparison being performed between the activationtimes of LV1 and LV4.

At block 230, I is again incremented by 1 causing I=4. At block 232, adetermination is made as to whether I=N. Since I=4 and N=4, then I=N.The YES path can be followed to block 234, which designates the optimalelectrode is LV1 since LV1 is the last remaining electrode that was noteliminated in the exhaustive electrode-pair comparisons. LV1 is thenselected as the final electrode for delivering CRT.

A second example shows how the selection is made when ED values of allelectrodes are almost equivalent or similar. For example, assume theorder of activation times during intrinsic rhythm (or RV only pacing)are such that AT(LV4)>AT(LV1)>AT(LV2)>AT(LV3). LV4 is associated withthe latest activation time and LV3 is associated with the earliestactivation time. From the biventricular pacing configurations, the EDvalues were determined such that ED(1)=30 ms, ED(2)=33 ms, ED(3)=25 ms,and ED(4)=28 ms. Referring to FIG. 6, ED data is retrieved for one LVelectrode such as ED(1) at block 208. At block 210, ED data is retrievedfor another LV electrode such as ED(2) at block 212. At block 212, thedifference in ED values is calculated follows:ED(2)−ED(1)=33 ms−30 ms=3 ms

At block 214, the difference in ED(1) and ED(2) is compared topredetermined threshold of 15 ms. As shown above, the difference inED(1) and ED(2) is only 3 ms which is less than the predeterminedthreshold of 15 ms. At block 216, a determination is made as to whetherthe difference in ED values is less than the threshold. Since thedifference is 3 ms is less than 15 ms, the YES path can be followed toblock 222 in which one AT (i.e. AT(1)) is compared to another AT (i.e.AT(2)). From the comparison, it was determined that AT(1) is greaterthan AT(2). At block 224, a NO path can be followed to block 228 thateliminates another electrode (i.e. LV2). At block 230, I is incrementedby I causing I=2. At block 232, a determination is made as to whetherI=N. Since I=2 and N=4, I does not equal N. Therefore, the NO pathreturns to block 210 in which another ED data (i.e. ED3) is retrievedfrom memory 82.

At block 212, the difference between ED(1) and ED(3) is calculated asfollows:ED(1)−ED(3)=30 ms−25 ms=5 ms

The difference in ED values of LV1 and LV3 is 5 ms which is less thanthe threshold value of 15 ms at block 216. The YES path can be followedto block 222 which compares AT(1) to AT(3). Since AT(3) is greater thanAT(1), the electrode LV3 is eliminated at block 228 based on its earlieractivation time compared to the electrode LV1. Again, I is incrementedby 1 at block 230 and another determination is made as to whether I=N atblock 232. Since I=3, I does not equal N. Therefore, another ED datasuch as ED(4) is retrieved from memory 82.

LV4 can then be compared with the electrode LV1. The difference in EDvalues of electrode LV1 and the electrode LV4 is 2 ms. At block 224, oneAT is found to be less than another AT. The electrode LV1 is eliminateddue to AT(LV1) having an earlier activation time compared to AT(4).Again, I is incremented by 1 causing I=4. Since I=N at block 232, theoptimal electrode is LV4. LV4 is chosen as the final or optimalelectrode from which to pace the LV since LV4 was not eliminated.

A third example is presented in which activation times during RV onlypacing or intrinsic rhythm of the four electrodes are such that

AT(LV4)>AT(LV1)>AT(LV2)>AT(LV3). Additionally, the ED values generatedfrom the biventricular pacing configurations are ED(1)=60 ms, ED(2)=40ms, ED(3)=38 ms, and ED(4)=62 ms. Referring to FIG. 6, processor 80retrieves ED(1) data and ED(2) data from memory 82 at blocks 208, 210,respectively. At block 212, the difference in ED values can becalculated by the following:ED(1)−ED(2)=60 ms−40 ms=20 ms

At block 216, since the difference in ED values associated with LV1 andLV2 is 20 ms which exceeds the threshold of 15 ms, the NO path can befollowed to block 218 in which the electrode with the higher ED value,i.e. electrode LV1 is eliminated. I is incremented by 1 at block 230. Adetermination is then made as to whether I=N at block 232. Since I=2,and N equals 4, the NO path returns to block 210 to retrieve ED(3) data.

At block 212, the difference in ED values can be calculated as follows:ED(3)−ED(2)=38 ms−40 ms=−2 ms

Since the difference in magnitude between ED(2) and ED(3) is 2 ms, whichis less than the threshold of 15 ms, the YES path can be followed toblock 222. At block 222, one AT (i.e. LV3) is compared to another AT(i.e. LV2). LV3 is associated with a AT that is less than the AT forLV2. At block 224, a determination is made as to whether one AT (i.e.LV3) is less than another AT (i.e. LV2). At block 226, electrode LV3 iseliminated.

Again, I is incremented by 1 at block 230. Therefore, I=3. At block 232,I does not equal N since I=3 and N=4; therefore, at block 210, ED(4) isretrieved from memory 82.

At block 212, the difference between ED(4) and ED(2) can be shown asfollows:ED(4)−ED(2)=62 ms−40 ms=22 ms

Since the difference in their ED values is 22 ms, well above thethreshold of 15 ms, the NO path can be followed to block 218. At block218, the electrode associated with the larger ED value is eliminated.Since ED(4) is larger (i.e. 62 ms) than ED(2) (i.e. 40 ms), LV4 iseliminated. I is again incremented by 1 at block 230 thereby causing Ito be equal to 4. At block 232, I=N; therefore, the YES path can befollowed to block 234. The optimal electrode is LV2. LV2 is then used topace the LV.

The method embodied in FIG. 6B is the same as FIG. 6A except block 225is replaced by block 227. As previously described relative to block 223,if one baseline AT is equal to the other baseline AT, then bothelectrodes are retained in a preference list. One of the two electrodescan be eliminated based upon additional or other criteria. For example,the pacing pulse can be automatically adjusted (e.g. increased ordecreased) at block 227. Equivalent electrodes are re-evaluated undermethod 200 by returning to block 202 using the new pacing criteria todetermine whether a difference exists between the two electrodes. Forexample, the pacing pulse can be increased by 0.25 volts, 0.5 volts,0.75 volts and so on. After rechecking the electrodes under method 200using the increased pacing pulse, more than likely, a difference willexist between the two electrodes and the electrode that under performsis eliminated. If not, the pacing criteria can again be modified and theelectrodes rechecked under method 200. The pacing criteria can becontinuously adjusted and the electrodes evaluated under method 200until a difference exists between the electrodes and one of theelectrodes can be eliminated. If one AT does not equal another AT, theNO path goes to block 224.

A set of LV electrode elimination rules can be summarized below whichcan be applied to scenarios in which an anatomic block is present or notpresent. An anatomic block is a difference between two AT that isgreater than a threshold T_(AT). One LV electrode elimination rule isthat when all electrodes have equivalent ED values, the LV electrodewith the latest activation during RV only pacing or intrinsic rhythm isselected for final CRT therapy. However, if one LV electrode isassociated with a higher ED compared to another LV electrode (i.e. adifference exceeding the predetermined threshold), the electrode withthe higher ED is eliminated as a possible choice, irrespective of theactivation times during intrinsic rhythm or RV only pacing.

Five examples are presented below in order to illustrate application ofrules for selecting an optimal LV electrode, including differentscenarios from simple ones when the LV lead in an area of electricallynormal tissue, to more complicated scenarios when the LV lead is acrossan area of anatomic block (for e.g. due to scar) or functional block.With respect to the five examples, assumptions were made. For example,lead 20 includes four LV electrodes such as LV1, LV2, LV3, and LV4.Additionally, the baseline activation times are determined during RVonly pacing or through intrinsic rhythm. It is further assumed that thebaseline activation times are ranked in the order such thatLV1>LV2>LV3>LV4, wherein LV1 is associated with the latest activationtime. Moreover, ED data is generated from biventricular pacingconfigurations. Pacing pulses for biventricular pacing configurationsrange from about 0.25 volts to about 8 volts and more preferably, aredelivered at 2 to 3 volts amplitude for both RV and LV pacing.

A first example or baseline involves the use of the LV lead 20 innormally conducting tissue with no functional or anatomic block. Thebaseline example can be used for comparative purposes with thesubsequent examples in which an anatomic block exists. Suppose theactivation times during, for example, intrinsic rhythm are sensed at LVelectrodes 1, 2, 3 and 4 are ranked in the order LV1>LV2>LV3>LV4, sothat LV1 is the latest activation time.

After the activation times have been determined, the ED data can begenerated for each biventricular pacing configuration. For example, a LVelectrode such as LV1 is selected to pace the LV by processor 80. Pacingpulses at 2 to 3 volts are delivered through LV1 to the LV while the RVelectrode simultaneously paces the RV.

The activation times for the LV electrodes are sensed in response to thebiventricular pacing of the LV and RV. AT(1) is equal to zero since LV1is used to pace the LV. The electrical ATs in the LV tissue are sensedand measured for each non-pacing LV electrode (e.g. LV2, LV3 and LV4).AT(2,3) was measured at 25 ms, while AT(4) was measured at 50 ms. Theequation for calculating ED as to LV1 is as follows:ED(1)=AT(1)+AT(2,3)+AT(4)/2=0+25+(50/2)=50 ms

LV2 was then selected and paced at 2 to 3 volts amplitude while the RVelectrode paces (e.g. at 2 to 3 volts amplitude) the RV. Electricalactivation times were measured at the non-pacing LV electrodes. AT(2,3)is equal to 0. AT(1) was measured at 25 ms, and AT(4) was measured at 25ms. The equation for calculating ED as to LV2 or LV3 is as follows:ED(2 or 3)=AT(1)+AT (2,3)+AT(4)=(25+0+25)ms=50 ms

LV4 was then paced while the RV electrode simultaneously deliveredpacing pulses to the RV. AT(4) is equal to zero since LV4 is used topace the LV. Electrical activation times were measured such that AT(1)equaled 50 ms, and AT(2,3) equaled 25 ms. The equation for calculatingED as to LV4 is as follows:ED(4)=AT(1)/2+AT(2,3)+AT(4)=(25+25+0)ms=50 ms

Since all ED values associated with each LV electrode are similar (e.g.difference between one ED value and another ED value equal to or lessthan a predetermined threshold such as 15 ms), the optimal pacing siteis located at the latest activation site in the LV during intrinsicrhythm or RV only pacing. Therefore, LV1 is the best or optimal LVelectrode from which to pace the LV. Table 1 presented below summarizesthe results.

Table 1 summarizes the biventricular pacing data for baseline example inwhich no block exists in the LV between the LV electrodes

Pacing electrode AT(1) ms AT(2,3) ms AT(4) ms ED ms LV1 0 25 50 50 LV2or LV3 25 0 25 50 LV4 50 25 0 50

A second example involves an anatomic block (e.g. a scar) located in theLV tissue between LV1 and LV2. As in the first example, the same orderof activation times generated during intrinsic rhythm is applied here.Since the order of activation times during intrinsic rhythm is known, EDdata generation is calculated according to the previously discussedbiventricular pacing configurations. In order to determine the ED data,processor 80 selects LV1 to deliver pacing pulses to LV tissue while theRV electrode paces the RV. Activation times were measured at the LVelectrodes in response to the biventricular pacing configuration. AT(1)is equal to zero since LV1 is used to pace the LV. Activation times weremeasured at LV2, LV3 and LV4. AT(2,3) was measured at 120 ms, and AT(4)at the LV4 was measured at 110 ms. The ED at LV1 is calculated asfollows:ED(1)=AT(1)+AT(2,3)+AT(4)/2=0+120+110/2=175 ms

LV2 and/or LV3 is selected to transmit pacing pulses to LV tissue.Electrical activation times were measured at electrodes LV2, LV3 andLV4. AT(2,3) is nearly equal to zero in this case (e.g. 5 ms) since LV3is very close to LV2 and the tissue between LV2 and LV3 conductsnormally. AT(1) was measured at 120 ms while AT(4) was measured at 25ms. The ED at LV2 is 150 ms and is calculated as follows:ED(2 or 3)=AT(1)+AT(2,3)+AT(4)=(120+5+25)ms=150 ms

LV4 is then selected to pace the LV while the RV electrode paces the RV.In response to LV4 transmitting pacing pulses to LV tissue, electricalactivation times were measured at LV1, LV2 or LV3. The AT(4) is equal tozero because LV4 is used to pace the LV. AT(1) at the LV1 was measuredat 120 ms, and AT(2,3) at LV electrodes 2,3 was measured at 25 ms. TheED at LV2 is 85 ms and is calculated as follows:ED(4)=AT(1)12+AT(2,3)+AT(4)=(120/2+25+0)ms=85 msLV4, physically located farthest from the anatomic block, produces an EDvalue that is less than the ED values of the other three LV electrodesby more than 15 ms. LV4 is the best or optimal LV electrode from whichto pace the LV. Table 2 summarizes pacing data that was obtained inwhich an anatomic block such as a scar exists in the LV tissue betweenLV1 and LV2.Table 2 summarizes pacing data for example 2 in which an anatomic blockexists between LV1 and LV2

Pacing electrode AT(1) ms AT(2,3) ms AT(4) ms ED ms LV1 0 120 110 175LV2 or LV3 120 5 25 150 LV4 120 25 0 85

A third example involves an anatomic block (e.g. a scar) located in thetissue between electrodes LV2 and LV3. Each biventricular pacingconfiguration is evaluated to generate ED data.

LV1 is selected to deliver pacing pulses to the LV while the RVelectrode simultaneously delivers pacing pulses to the RV. In responseto biventricular pacing, activation times were measured at LV2, LV3 andLV4. AT(1) is equal to zero since LV1 is used to pace the LV. AT(2) wasmeasured at 25 ms, and AT(3) at LV3 was measured at 125 ms. Therefore,AT(2,3)=[(25+125)/2]ms=75 ms and AT(4) is 100 ms. The ED at LV1 iscalculated as follows:ED(1)=AT(1)+AT(2,3)+AT(4)/2=0+75+100/2=125 ms

LV2 is then paced while the RV electrode paces the RV. The AT(2) is zerosince LV2 is used to pace the LV. In response to biventricular pacing,electrical activation times were measured at LV1, LV3 and LV4. AT(1) wasmeasured at 25 ms, AT(3) at the LV3 was measured at 125 ms, and AT(4) atthe LV4 was measured at 100 ms. AT(2,3)=(0+125)/2=62.5 ms. The ED at LV2is 187.5 ms and is calculated as follows:ED(2)=AT(1)+AT(2,3)+AT(4)=(25+62.5+100)ms=187.5 ms

LV3 is then paced while the RV electrode simultaneously paces the RV.AT(3) is zero since LV3 is used to pace the LV. In response to LV3transmitting pacing pulses to LV tissue, AT were measured at LV1, LV2,and LV4. AT(1) was measured at 100 ms, AT(2) was measured at 125 ms, andAT(4) was measured at 25 ms. The ED at LV3 is calculated as follows:ED(3)=AT(1)+AT(2,3)+AT(4)=(100+62.5+25)ms=187.5 ms

LV4 is then selected to deliver pacing pulses to the LV while the RVelectrode paces the RV. The AT(4) is zero since LV4 is used to pace theLV. Activation times were measured at LV1, LV2, and LV3. AT(1) wasmeasured at 100 ms, AT(2) is 125 ms, and AT(3) was measured at 25 ms.AT(2,3)=75 ms since AT(2,3)=(125+25)ms/2=150 ms/2. The ED at LV4 iscalculated as follows:ED(4)=AT(1)/2+AT(2,3)+AT(4)=(100/2+75+0)ms=125 msThe pattern of electrical activation is more favorable for LV1 and LV4since ED(1)=ED(4). LV1 is selected for pacing the LV since the tissuenear LV1 exhibits the latest activation time during intrinsic activationor RV only pacing. Table 3, presented below, shows the pacing data forthe anatomic block between LV2 and LV3.

TABLE 3 summary of the pacing data for example 3 where an anatomic blockexists between LV2 and LV3 Pacing electrode AT(1) ms AT(2) ms AT(3) msAT(4) ms ED ms LV1 0 25 125 100 125 LV2 25 0 125 100 187.5 LV3 100 125 025 187.5 LV4 100 125 25 0 125

Another example relates to an anatomic block (e.g. a scar) located inthe LV tissue between LV3 and LV4. LV1 is selected to pace the LV whilethe RV electrode paces the RV. AT(1) is equal to zero since LV1 is usedto pace the LV. In response to biventricular pacing, activation timeswere measured at LV2, LV3 and LV4. AT(2,3) was measured at 27.5 ms, andAT(4) was measured at 125 ms. ED(1) at LV1 is calculated as follows:ED(1)=AT(1)+AT(2,3)+AT(1)/2=[0+27.5+(125/2)]ms=90 ms

LV2 or LV3 is then selected to pace the LV while the RV electrode pacesthe RV. The AT(2,3) is equal to 5 ms but is expected to be equal to zerosince LV2 is used to pace the LV. In pacing of the LV and RV, electricalactivation times were measured at LV1, LV3 and LV4. AT(1) was measuredat 25 ms, and AT(4) was measured at 125 ms. The ED at LV2 is 150 ms andis calculated as follows:ED(2)=AT(1)+AT(2,3)+AT(4)=(25+5+120)ms=150 ms

Pacing from LV3 creates an identical ED since LV2 and LV3 are closelyspaced and tissue between LV2 and LV3 conduct normally. Therefore,ED(3)=150 ms.

LV4 is then selected to pace the LV while the RV electrode paces the RV.In response to biventricular pacing pulses, AT were measured at LV1, andLV(2, 3) but no activation time was measured at AT(4) since LV4 is usedto pace the LV. AT(1) is 100 ms, and AT(2,3) at LV(2, 3) was measured at122.5 ms. The ED at LV2 is 172.5 ms and is calculated as follows:ED(4)=AT(1)/2+AT(2,3)+AT(4)=(100/2+122.5+0)ms=172.5 ms

The pacing data for this example is presented in Table 4.

TABLE 4 Summary of pacing data for example 4 in which an anatomic block(e.g. scar) exists between LV3 and LV4 Pacing electrode AT(1) ms AT(2,3)ms AT(4) ms ED ms LV1 0 27.5 125 90 LV2 or LV3 25 5 125 150 LV4 100122.5 0 172.5Typically, the LV electrode that is most distal to the anatomic blockachieves increased resynchronization between the LV and the RV.Accordingly, LV1 is the best electrode from which to pace. LV4 is theworst LV electrode from which to pace because LV4 completely blocksactivation of the LV tissue. Additionally, pacing from LV2 or LV3 isworse than LV1.

A fifth example relates to a unidirectional functional block that existsbetween LV1 and LV2 while pacing from LV1 but is absent while pacingfrom LV2, LV3 or LV4. In response to LV1 biventricular pacing pulsesbeing delivered to the RV and the LV, electrical activation times weremeasured at LV2, LV3 and LV4. The AT(1) is equal to zero since LV1 isused to pace the LV. AT2,3 was measured at 122.5 ms, and AT(4) wasmeasured at 100 ms. The ED at LV1 is calculated as follows:ED(1)=AT(1)+AT(2,3)+AT(4)/2=(0+100/2+122.5)ms=172.5 ms

LV2 or LV3 is then selected to pace the LV while the RV electrode pacesthe RV. In response to this biventricular pacing configuration,activation times were measured at electrodes 1, 3 and 4. AT(2,3) isnearly zero (e.g. 5 ms) since LV2 is used to pace the LV. AT(1) at theLV1 was measured at 25 ms, and AT(4) was measured at 25 ms. The ED atLV2 is 55 ms and is calculated as follows:ED(2)=AT(1)+AT(2,3)+AT(4)=(25+5+25)ms=55 msSince LV3 is closely spaced to LV2, the tissue between LV2 and LV3conducts normally. Therefore, pacing from LV3 creates an identical ED toLV2. Specifically, ED(3)=55 ms.

LV4 is then selected to pace the LV while the RV electrode paces the RV.In response to LV4 delivering pacing pulses to LV tissue, AT weremeasured at LV1, and electrodes 2, 3. The AT4 is equal to zero becauseLV4 is used to pace the LV. AT(1) at the LV1 was measured at 50 ms, andAT(2,3) at LV 2,3 was measured at 22.5 ms. The ED at LV2 is 47.5 ms andis calculated as follows:ED(4)=AT(1)/2+AT(2,3)+AT(4)=(50/2+22.5+0)ms=47.5 msED(2) or ED(3) and ED(4) are similar (i.e. less than 15 ms); therefore,LV2 or LV3 can be selected to pace the LV since each of these electrodesare associated with an activation times that are later than LV4. Thepacing data for anatomic block between LV3 and LV4 is presented in Table5.

TABLE 5 Summary of the pacing data for example 5 in which an anatomicblock exists between LV3 and LV4 Pacing electrode AT(1) ms AT(2,3) msAT(4) ms ED ms LV1 0 122.5 100 172.5 LV2 or LV3 25 5 25 55 LV4 50 22.5 047.5

The sixth example relates to LV4 that is located in or on scarred LVtissue that does not capture. In the first biventricular pacingconfiguration, LV1 is used to pace the LV. AT(1) is equal to zero sinceLV1 is used to pace the LV. In response to LV1 delivering pacing pulsesto LV tissue, activation times were measured at LV2, LV3 and LV4.AT(2,3) at the LV2 was measured at 25 ms, and AT(4) was measured at 150ms. The ED at LV1 is calculated as follows:ED(1)=AT(1)+AT(2,3)+AT(4)/2=[0+25+(150/2)]ms=100 ms

LV2 or LV3 are then paced. In response to LV2 or LV3, transmittingpacing pulses to LV tissue, electrical activation times were measured atLV1, LV3 and LV4. AT(2,3) is nearly zero (e.g. 5 ms) since LV2 is usedto pace the LV. AT(1) was measured at 25 ms, and AT(4) was measured at150 ms. The ED at LV2 is 180 ms and is calculated as follows:ED(2)=AT(1)+AT(2,3)+AT(4)=(25+5+150)ms=180 msSince LV3 is closely spaced to LV2, and tissue between LV2 and LV3conducts normally and ED(3)=ED(2)=180 ms.

Table 6, presented below, summarizes all the data obtained from theexamples 1-5.

TABLE 6 Summary of pacing data related to anatomic blocks in LV tissueAT(1) Milli- AT AT AT Pacing seconds (2, 3) (3) (4) ED Scenarioelectrodes (ms) ms ms ms ms Scenario 1 LV 1 and 0 25 ms 50 50 (baseline)RV electrode No block LV 2 or 25 5 25 55 between LV3 and electrodes RVelectrode LV 4 and 50 25 0 50 RV electrode Scenario 2 LV 1 and 0 120 110175 Anatomic RV electrode block located LV 2 and 120 5 25 150 in thetissue RV electrode between LV 4 and 120 25 0 85 electrodes 1 RVelectrode and 2 Scenario 3 LV 1 and 0 25 125 100 125 Anatomic RVelectrode block located LV 2 and 25 0 125 100 187.5 in the tissue RVelectrode between LV 3 and 100 125 0 25 187.5 electrodes LV RV electrodeelectrodes 2 LV 4 and 100 125 25 0 125 and 3 RV electrode Scenario 4 LV1 and 0 27.5 125 90 Anatomic RV electrode block located LV 2 and 25 5125 150 in the tissue RV electrode between LV 4 and 100 122.5 0 172.5electrodes LV RV electrode electrodes 3 and 4 Scenario 5 LV 1 and 0122.5 100 172.5 Unidirectional RV electrode functional LV 2 and 25 5 2555 block between RV electrode 1 and 2 while LV 4 and 50 22.5 0 47.5pacing from 1 RV but absent while pacing from 2(3) or 4

While the five examples presented above employed a quadripolar lead withthe previously specified inter-electrode distances, skilled artisansappreciate that the same principle of weighted electrical dyssynchronymeasures could be applied with different weighted values differentinter-electrode spacings on a lead. The weighted values are modifiedaccording to the relative distances of each electrode from the pacingelectrode. For example, if the LV electrodes on a LV lead are allequidistant, then formula for the weighted electrical dyssynchrony wouldbe modified as follows:ED(1)=AT(1)+AT(2)+AT(3)/2+AT(4)/3ED(2)=AT(1)+AT(2)+AT(3)+AT(4)/2ED(3)=AT(1)/2+AT(2)+AT(3)+AT(4)/2 andED(4)=AT(1)/3+AT(2)/2+AT(3)+AT(4).

In one or more embodiments, once an optimal LV electrode is chosen, anoptimal delay such as A-V delay (A) and/or V-V delay (D) can bedetermined through exemplary methods 300 or 400 presented in flowdiagrams of FIGS. 7-8, respectively.

In one or more embodiments, once an optimal LV electrode is chosen, anoptimal A-V delay can be determined through an exemplary method 300presented in flow diagrams of FIG. 7, respectively. In one or moreembodiments, A-V delay optimization occurs in a similar manner as thatwhich was performed to select the optimal LV electrode from which topace. In one or more embodiments, A-V delay optimization can beperformed through a use of a weighted sum of activation times forvarious A-V delays. The A-V delay that results in the lowest electricaldyssynchrony is selected and programmed into the programmer 24.

In order to determine the optimal A-V delay, an ED must be calculatedfor at least two or more A-V delays with a nominal value of V-V delay D.For example, D can be set to 0. Thereafter, ED(j, A) represents theelectrical dyssynchrony during simultaneous biventricular pacing from RVelectrode and LV electrode j. “A” represents an A-V delay and AT(i, A)represents activation time at LV electrode i during biventricularpacing.

ED that includes a A-V delayED(j,A)=Σ_(i=1) ^(n) w(i,j)AT(i,A)“n” is the total number of LV electrodes.D is zero for the present example; however, skilled artisans appreciatethat alternative embodiments are contemplated in which the V-V delay (D)is non-zero. Generally, as long as V-V delay is fixed at a constantvalue (e.g. zero, nonzero, nominal value), an optimal A-V delay can beadequately determined.

As previously stated, only valid ED are used to determine an optimal LVelectrode from which to pace. Negative values for one or more AT(i) orvalues in which either LV or RV or both LV and RV do not capture areomitted. The programmer 24 can automatically choose A-V delays rangingfrom a lowest value of 40 ms to a highest value of 260 ms, in incrementsof 5, 10, 15 or 20 ms for atrial sensing. The same values are alsoselected during atrial pacing.

After selecting the A-V delays, the programmer 24 causes the pulsegenerator to generate pacing pulses (e.g. ranging from about 0.25 voltsto about 8 volts and more preferably, between 2-3 volts) that aredelivered through the optimal LV electrode to the LV while other pacingpulses (e.g. ranging from about 0.25 volts to about 8 volts and morepreferably, between 2-3 volts) are transmitted through the RV electrodeto the RV at operation 302. The physiological response to the pacingpulses can be observed.

After measuring the electrical activation times at non-pacing electrodesat operation 304, the microprocessor 80 determines electricaldyssynchrony index for the first A-V delay using the ED equation aboveassociated with the optimal LV pacing electrode at operation 306. Forexample, the weighted sum equation could take into account the physicalspacing, as previously discussed, between the LV electrodes on the LVlead 20. For example, the electrical dyssynchrony metric forsimultaneous biventricular pacing from RV and LV1 electrode at a A-Vdelay of 40 ms can be expressed as follows:ED(1,40)=AT(1,40)+AT([2,3],40)+AT(4,40)/2 whereinAT([2,3],40)=[AT(2,40)+AT(3,40)]/2

Since LV2 and LV3 are substantially close, the AT of LV2 and LV3 areaveraged together. The AT associated with LV4 is muliplied by a constantnumber w(i, j). W(i, j) is a weighing factor that depends on thedistance from LV1 to LV4 as compared to the distance between LVelectrodes (2,3) and LV1. In this example, w(4,1) is ½ since thedistance from LV1 to LV4 is twice as long as distance from electrodes(2,3) to LV1. W(i, j) can be adjusted depending upon the LV medicalelectrical lead and the spacing used between the plurality of electrodesthereon.

The ED equation that is used to calculate the weighted electricaldyssynchrony index for a given value A-V delay depends on the optimal LVelectrode that is selected. For example, if LV1 is the optimal LVelectrode, then ED(1) is used to calculate the ED for each of the A-Vdelays that are being tested. If LV2 is the optimal LV electrode thenED(2) is used to calculate and optimize the A-V delay. If LV3 is theoptimal LV electrode then ED(3) is used to calculate and optimize theA-V delay. If LV4 is the optimal LV electrode then ED(4) is used tocalculate and optimize the A-V delay.

After an ED has been determined for the first A-V delay, the programmer24 automatically selects a second A-V delay. Again, pacing pulses aredelivered through the RV electrode and the LV electrode at a second A-Vdelay while the sensing LV electrodes sense at operation 308. Theactivation times for the non-pacing LV electrodes are then measured forthe second A-V delay at operation 310. The EDI for the second A-V delayis calculated at operation 312 using the same ED equation that was usedto calculate the ED for the first A-V delay. After determining thesecond ED for a second A-V, the programmer 24 automatically selects athird A-V delay and then the programmer 24 sends pacing pulses to the RVelectrode and/or the LV electrode. A third ED is then calculated for thethird A-V delay. After the third ED is calculated, the programmer 24automatically calculates up to N number of A-V delays. Typically, theprogrammer 24 automatically tests N (e.g. N can be 12-20 etc.) number ofsensed A-V delays and M number of paced A-V delays for a restingcycle-length (e.g. time (ms) between two events such as successiveatrial events). Typically N equals M, although skilled artisans willunderstand that N does not have to be equal to M since determining EDvalues for sensed A-V delays is a different operation than paced A-Vdelays. Generally, the programmer 24 tests less than 100 A-V delays. Inone or more other embodiments, programmer 24 can automatically test 20or less A-V delays. In yet another embodiment, programmer 24 canautomatically test 10 or less A-V delays. Negative A-V delays are nottested because pre-excitation of ventricles before the atrial activationis not hemodynamically optimal.

Table 7, presented below, provides an example of ED results for SA-Vdelays that ranges from a short delay (i.e. 40 ms) to a long delay (i.e.260 ms). Each A-V delay is automatically separated by predetermined timeincrements (i.e. 20 ms) although other suitable time incremental values(e.g. 5 ms, 10 ms, 15 ms etc.) can also be used. Biventricular pacingfrom LV1 and RV electrodes performed using a particular A-V delay, whilemaintaining the V-V delay at a constant or fixed nominal value allowsexemplary data to be generated for Table 7. The A-V delay that providesa minimum ED is selected as an optimal A-V delay. In this example, theoptimal A-V delay is 180 ms that corresponds to a minimum ED.

TABLE 7 ED for a range of sensed A-V (SA-V) delays at resting heart rateSA-V delay (ms) 40 60 80 100 120 140 160 180 200 220 240 260 ED(ms) 2929 29 28 28 26 26 24 27 28 28 34In a situation in which two or more A-V delays have the same minimum ED,the lowest A-V delay is selected as the optimal A-V delay.

To evaluate an optimal A-V delay changes during atrial pacing, atrialpacing is initiated at a rate equal to or just above the patient'sresting sinus rate. Table 8 summarizes paced A-V delays (PAV) that havebeen computed using a similar method as that which is described relativeto SAV. The optimal PAV in this case is 200 ms.

The ΔAV_(rest) is the difference between optimal PAV and optimal SAV andis noted as follows:ΔAV _(rest)=optimal PAV−optimal SAV=(200−180)ms=20 ms.

Atrial pacing can also be initiated at decreasing cycle-lengths in stepsof 50 ms from the resting cycle-length. The same procedure can berepeated in order to identify the optimal PAV at each cycle-length. Forexample, the lowest ED is identified and then the corresponding PA-V isselected. The corresponding optimal SAV for each cycle-length may be setby subtracting ΔAV_(rest) from the optimal PAV at that cycle-length. Therange of cycle-lengths covered in this manner may start from the restingcycle-length and end in the upper atrial tracking rate.

TABLE 8 ED for a range of PAV delays at atrial pacing with cycle- lengthequal or just above the resting heart rate PA-V delay (ms) 40 60 80 100120 140 160 180 200 220 240 260 ED (ms) 31 29 29 29 28 28 27 27 25 26 2928

Table 9 is a look-up table of optimal PAV and SAV values for differentcycle-lengths that can be used for optimal and dynamic adaptation of A-Vdelay corresponding to different sensed or paced cycle-lengths. Inparticular, A-V optimization can automatically adjust A-V delaysaccording to changes in heart rates (e.g. faster heart or lowercycle-lengths). The programmer 24 or IMD 16 can adjust the AV delay byusing the look-up table that relates cycle length, PAV and/or SAV. Forexample, the IMD 16 can easily adjust the AV delay (whetheratrial-sensed or atrial-paced) according to the detected currentcycle-length. Referring briefly to Table 9, cycle length 750 mscorresponds to a PAV of 180 ms and a SAV of 160 ms. Accordingly, the PAVcan be adjusted or the SAV can be adjusted to the designated optimumlevels.

Table 9 is automatically generated by the programmer 24 and stored intomemory. Programmer 24, for example, can initiate atrial pacing atdifferent rates. The optimal PAV can be determined and stored intomemory for a given atrial pacing rate. The corresponding optimal SAV canbe determined for the same rate by subtracting ΔAV_(rest) as previouslydiscussed and storing the optimal SAV value for that rate.

Table 9 is a look-up table of optimal PAV and SAV for differentcycle-lengths from resting (1000 ms) to upper tracking rate (500 ms)

Cycle length (CL) Optimum PAV Optimum SAV (ms) (ms) (ms) 1000 200 180950 200 180 900 200 180 850 200 180 800 180 160 750 180 160 700 180 160650 160 140 600 160 140 550 140 120 500 140 120

After A-V delay has been optimized, the V-V delay undergoes theoptimization process. V-V optimization occurs in a similar manner asthat which was performed to select the optimal LV electrode from whichto pace. In one or more embodiments, V-V optimization can be performedthrough a use of a weighted sum of activation times for various V-Vdelays and the V-V that results in the lowest activation time isselected and programmed into the programmer 24.

In order to determine the optimal V-V delay, an ED must be calculatedfor two or more V-V delays with the A-V delay set to optimal valueA_(opt).

ED that includes a V-V delay such thatED(j,Aopt,D)=Σ_(i=1) ^(n) w(i,j)AT(i,Aopt,D)

As previously stated, only valid ED are used to determine an optimal LVelectrode from which to pace. Negative values for one or more AT(i) orinstances where RV or LV or both RV and LV does not capture are omitted.

The first V-V delay can be any amount of delay that the programmer 24automatically selects for a particular patient. Alternatively, theprogrammer 24 can be automatically set to perform increments of delayssuch as 5 ms delay, 10 ms, 15 ms . . . 100 ms delay etc. Generally,introducing a V-V delay can depend on the patient's physiology (e.g.age, size, gender etc.). Either a right ventricle to left ventricledelay or a left ventricle to right ventricle delay can be input in tothe programmer 24 by the user. The programmer 24 can automatically beginto introduce, for example, a 80 ms delay between the right ventricle andthe left ventricle.

After selecting the V-V delay, the programmer 24 causes the pulsegenerator to generate pacing pulses (e.g. ranging from about 0.25 voltsto about 8 volts and more preferably, between 2-3 volts) that aredelivered through the optimal LV electrode to the LV while other pacingpulses (e.g. ranging from about 0.25 volts to about 8 volts and morepreferably, between 2-3 volts) are transmitted through the RV electrodeto the RV at operation 402. The physiological response to the pacingpulses can be observed.

After measuring the electrical activation times at non-pacing electrodesat operation 404, the microprocessor 80 determines electricaldyssynchrony index for the first V-V delay using the equation aboveassociated with the optimal LV pacing electrode at operation 406. Forexample, the weighted sum equation could take into account the physicalspacing, as previously discussed, between the LV electrodes on the LVlead 20. For example, the electrical dyssynchrony during biventricularpacing from RV electrode and LV1 electrode, with A-V delay betweenatrial (sensed or paced) signal and the first ventricular pacing pulseset to the optimal value A_(opt) can be expressed as follows:ED(1,A _(opt),40)=AT(1,A _(opt),40)+AT([2,3],A _(opt),40)+AT(4,A_(opt),40)/2 where AT([2,3],A _(opt),40)=[AT(2,A _(opt),40)+AT(3,A_(opt),40)]/2

Since electrodes 2 and 3 are substantially close, the AT of electrodes 2and 3 are averaged together. The AT associated with LV4 is divided by aconstant number W. W is the distance from LV1 to LV4 as compared to LVelectrodes (2,3) to 1. In this example, W is 2 since the distance fromLV1 to LV4 is twice as long as distance from electrode (2,3) to LV1. Wcan be adjusted depending upon the LV medical electrical lead and thespacing used between the plurality of electrodes thereon.

The ED equation that is used to calculate the weighted electricaldyssynchrony index for a given value V-V delay depends on the optimal LVelectrode that is selected. For example, if LV1 is the optimal LVelectrode, then ED(1) is used to calculate the ED for each of the V-Vdelays that are being tested. If LV2 is the optimal LV electrode thenED(2) is used to calculate and optimize the V-V delay. If LV3 is theoptimal LV electrode then ED(3) is used to calculate and optimize theV-V delay. If LV4 is the optimal LV electrode then ED(4) is used tocalculate and optimize the V-V delay.

After an ED has been determined for the first V-V delay, the programmer24 automatically selects a second V-V delay. Again, pacing pulses aredelivered through the RV electrode and the LV electrode at a second V-Vdelay while the sensing LV electrodes sense at operation 408. Theactivation times for the non-pacing LV electrodes are then measured forthe second V-V delay at operation 410. The EDI for the second V-V delayis calculated at operation 412 using the same ED equation that was usedto calculate the ED for the first V-V delay. After determining thesecond ED for a second V-V, the programmer 24 automatically selects athird V-V delay and then the programmer 24 sends pacing pulses to the RVelectrode and/or the LV electrode. A third ED is then calculated for thethird V-V delay. After the third ED is calculated, the programmer 24 cancalculate up to N number of V-V delays. Typically, the programmer 24will test less than 100 V-V delays. In one or more other embodiments,the programmer 24 can test 20 or less V-V delays. In yet anotherembodiment, the programmer 24 can test 10 or less V-V delays.

After introducing a variety of V-V delays, a V-V delay is selected thatproduces the least ED at operation 414. If there are more than one V-Vdelays that produces the least ED, then V-V delay with the minimumabsolute value would be programmed into the implantable medical deviceas the baseline V-V delay for the patient. For example, if the two V-Vdelays producing the least electrical dyssynchrony index are Oms(simultaneous biventricular pacing) and −10 ms (LV pacing ahead of RV by10 ms), then the programmed V-V delay would be Oms.

V-V is optimization is illustrated through scenario three presented inTable 6 in which LV1 was selected as the optimal electrode for CRTtherapy based on ED values during simultaneous biventricular pacing (V-Vdelay=0). The ED(1) equation was used to calculate ED at various V-Vdelays. ED measurements can be performed by the programmer 24 duringpacing from RV electrode and pacing from the optimal electrode(electrode 1) on the LV by introducing variable V-V delays from −50 ms(LV pacing 50 ms ahead of RV pacing) to +50 ms (LV pacing 50 ms after RVpacing) at intervals of 10 ms. Table 11, presented below, summarizes EDmeasurements (in ms) with variable V-V delays (in ms) for scenario three(summarized in Table 6) during pacing from RV electrode and pacing fromthe optimal LV electrode (LV1).

The minimum ED value is obtained at a V-V delay of −20 ms which is setas the optimal V-V delay for this case.

Table 11, presented below, includes exemplary data for biventricularpacing using a plurality of V-V delays.

TABLE 11 Biventricular pacing data using a set of V-V Delays V-V (ms)−50 −40 −30 −20 −10 0 10 20 30 40 50 ED (ms) 162 151 135 105 110 125 125130 146 155 150

Either before or after optimizing the A-V delay and the V-V delay, adetermination can be made as to whether one of the leads should berepositioned. For example, after the ED data has been obtained for eachLV electrode (e.g. LV1, LV2, LV3, and LV4), then the ED data can becompared to a threshold (e.g. 60 ms). In one or more embodiments, asimple criteria on the LV activation times during RV pacing or intrinsicrhythm can be used to determine if the LV lead 20 should be moved. Forexample, if the LV activation times are less than 60 ms, then the lead20 should be moved or that electrode should not be paced. This simplecriterion could be added to any of the above criteria for selecting apacing vector.

While the invention has been described in its presently preferred form,it will be understood that the invention is capable of modificationwithout departing from the spirit of the invention as set forth in theappended claims. For example, in one or more embodiments, two or more LVelectrodes may be selected for multi-site pacing of the LV. An exampleof such a configuration may be seen with respect to U.S. Pat. No.6,804,555 issued Oct. 12, 2004, and assigned to the assignee of thepresent invention, the disclosure of which is incorporated by referencein its entirety herein. Moreover, while the electrodes have beendescribed as being able to either sense or pace, skilled artisansappreciate that other embodiments can employ electrodes that are able toboth sense and pace. Additionally, many different medical electricalleads can be used to implement one or more embodiments. For example, StJude's Quartet™ Quadripolar, left-ventricular pacing lead or BostonScientific's EASYTRAK left ventricular pacing/sensing lead can be used.

The techniques described in this disclosure, including those attributedto the IMD 16, the programmer 24, or various constituent components, maybe implemented, at least in part, in hardware, software, firmware, orany combination thereof. For example, various aspects of the techniquesmay be implemented within one or more processors, including one or moremicroprocessors, DSPs, ASICs, FPGAs, or any other equivalent integratedor discrete logic circuitry, as well as any combinations of suchcomponents, embodied in programmers, such as physician or patientprogrammers, stimulators, image processing devices, or other devices.The term “module,” “processor,” or “processing circuitry” may generallyrefer to any of the foregoing logic circuitry, alone or in combinationwith other logic circuitry, or any other equivalent circuitry.

Such hardware, software, and/or firmware may be implemented within thesame device or within separate devices to support the various operationsand functions described in this disclosure. In addition, any of thedescribed units, modules, or components may be implemented together orseparately as discrete but interoperable logic devices. Depiction ofdifferent features as modules or units is intended to highlightdifferent functional aspects and does not necessarily imply that suchmodules or units must be realized by separate hardware or softwarecomponents. Rather, functionality associated with one or more modules orunits may be performed by separate hardware or software components, orintegrated within common or separate hardware or software components.

Skilled artisans also appreciate that the exemplary methods presented inthe flow diagrams are intended to illustrate the general functionaloperation of the devices described herein, and should not be construedas reflective of a specific form of software or hardware necessary topractice all of the methods described herein. It is believed that theparticular form of software will be determined primarily by theparticular system architecture employed in the device (e.g., IMD 16,programmer 24) and by the particular detection and therapy deliverymethodologies employed by the device and/or system. Providing softwareand/or hardware to accomplish the described methods in the context ofany modern IMD or programmer, given the disclosure herein, is within theabilities of one of skill in the art.

When implemented in software, the functionality ascribed to the systems,devices and techniques described in this disclosure may be embodied asinstructions on a computer-readable medium such as RAM, ROM, NVRAM,EEPROM, FLASH memory, magnetic data storage media, optical data storagemedia, or the like. The instructions may be executed by one or moreprocessors to support one or more aspects of the functionality describedin this disclosure. It is appreciated that the LV electrodes can beplaced at locations about and/or along the LV. It is also appreciatedthat more than four LV electrodes can be used to monitor electricalactivation times.

Furthermore, it is understood that ED is a function of multiplevariables such as pacing electrode, A-V delay, and V-V delay.Optimization of ED is based on any one variable while keeping the othervariables at a constant value. Additionally, other embodiments arecontemplated in which a physician may optionally perform one or moreoperations for any methods described herein.

This disclosure has been provided with reference to illustrativeembodiments and is not meant to be construed in a limiting sense. Asdescribed previously, one skilled in the art will recognize that othervarious illustrative applications may use the techniques as describedherein to take advantage of the beneficial characteristics of theapparatus and methods described herein. For example, it is contemplatedthat other embodiments could use electrodes that are configured to paceand sense. Various modifications of the illustrative embodiments, aswell as additional embodiments of the disclosure, will be apparent uponreference to this description.

What is claimed:
 1. A method of cardiac pacing employing a rightventricular electrode and a plurality of left ventricular electrodes,comprising: a) pacing using the right ventricular electrode and a pacingleft ventricular electrode using a first A-V delay; b) measuringactivation times at other ones of the left ventricular electrodes inresponse to pacing the right ventricular electrode and a pacing leftventricular electrode; c) determining a weighted electrical dyssynchronyassociated with the first A-V delay; d) pacing using the rightventricular electrode and the pacing left ventricular electrodes using asecond A-V delay; e) measuring activation times at other ones of theleft ventricular electrodes the right ventricular electrode and a pacingleft ventricular electrode; and f) determining a weighted electricaldyssynchrony for the second A-V delay; g) comparing weighted electricaldyssynchrony for the first and the second A-V delays; and h) selectingan optimal A-V delay in response to comparing weighted electricaldyssynchrony for the first and the second A-V delays, wherein theweighted electrical dyssynchrony is determined using${{ED}\left( {I,A,D} \right)} = {\sum\limits_{i = 1}^{n}{{w\left( {1,I} \right)}{{AT}\left( {1,A,D} \right)}}}$ wherein factor w(i, j) is a distance of a sensing electrode I from apacing electrode, n is a total number of left ventricular electrodes,atrio-ventricular delay, and D is a time delay between pacing pulses ina right ventricle and a left ventricle.
 2. The method of claim 1 whereinthe weighted electrical dyssynchrony includes a weighting factorassociated with each of the electrodes of the left ventricularelectrodes, each weighting factor based on each electrode's distancefrom the pacing electrode.
 3. The method of claim 1 further comprising:averaging activation times associated with the first one when two ormore of the left ventricular electrodes are substantially close; andaveraging activation times associated with the second one when two ormore of the left ventricular electrodes are substantially close.
 4. Themethod claim 3, wherein substantially close is within about 1.5 mm. 5.The method of claim 1 further comprising: determining that the optimalA-V delay is associated with a lowest value of weighted electricaldyssynchrony.
 6. The method of claim 5 further comprising determiningthat the optimal A-V delay is associated with a smallest value A-V delayif the first and second A-V delays are associated with equal values ofelectrical dyssynchrony.
 7. The method of claim 6 further comprising:determining a weighted electrical dyssynchrony for N number of A-Vdelays; and comparing weighted electrical dyssynchrony for the N A-Vdelays, wherein N is any number between 2 and
 100. 8. The method ofclaim 7 wherein the optimal A-V delay is a last remaining A-V delay thathas not been eliminated out of N A-V delays.
 9. The method of claim 1further comprising: eliminating either the first or the second A-Vdelays whichever A-V delay is associated with a greater value ofelectrical dyssynchrony.
 10. The method of claim 1 further comprising:eliminating either the first A-V delay or the second A-V delay basedupon whichever A-V delay has a greater value when the weightedelectrical dyssynchrony for the first and the second A-V delays areequal.
 11. The method of 10 wherein the first and second A-V delay areassociated with atrial sense at a resting atrial rate.
 12. The method ofclaim 11 wherein the resting atrial rate is between about 50 to about 75beats per minute.
 13. The method of claim 10 wherein the first andsecond A-V delay are associated with atrial pacing performed at a rategreater than or equal to a resting atrial rate and less than or equal toa programmed atrial upper tracking rate.
 14. The method of claim 13wherein determining ΔAV_(rest) by subtracting an optimal sensed A-Vdelay from an optimal paced A-V delay.
 15. The method of claim 14wherein the optimal paced A-V delay is determined for each of N numberof atrial pacing rates above the resting atrial rate but less than orequal to a programmed atrial upper tracking rate.
 16. The method ofclaim 15 further comprising determining an optimal sensed A-V delay foreach corresponding atrial rate.
 17. The method of claim 16 wherein theoptimal sensed A-V delay is determined by subtracting ΔAV_(rest) fromthe optimal paced A-V delay.
 18. The method of claim 16 wherein numberranges from 2-100.
 19. The method of claim 16 wherein a look-up table ofoptimal paced and sensed A-V delays for different atrial rates may bestored and paced and sensed A-V delays are adapted accordingly inresponse to changes in the atrial rates during subsequent delivery ofcardiac resynchronization therapy.
 20. A system of cardiac pacingemploying a right ventricular electrode and a plurality of leftventricular electrodes, comprising: a) means for pacing using the rightventricular electrode and a pacing left ventricular electrode using afirst A-V delay; b) means for measuring activation times at other onesof the left ventricular electrodes in response to pacing the rightventricular electrode and a pacing left ventricular electrode; c) meansfor determining a weighted electrical dyssynchrony associated with thefirst A-V delay; d) means for pacing using the right ventricularelectrode and the pacing left ventricular electrodes using a second A-Vdelay; e) means for measuring activation times at other ones of the leftventricular electrodes the right ventricular electrode and a pacing leftventricular electrode; f) means for determining a weighted electricaldyssynchrony for the second A-V delay; g) means for comparing weightedelectrical dyssynchrony for the first and the second A-V delays; and h)means for selecting an optimal A-V delay in response to comparingweighted electrical dyssynchrony for the first and the second A-Vdelays, wherein the weighted electrical dyssynchrony is determined using${{ED}\left( {I,A,D} \right)} = {\sum\limits_{i = 1}^{n}{{w\left( {1,I} \right)}{{AT}\left( {1,A,D} \right)}}}$ wherein factor w(i, j) is a distance of a sensing electrode I from apacing electrode, n is a total number of left ventricular electrodes,atrio-ventricular delay, and D is a time delay between pacing pulses ina right ventricle and a left ventricle.
 21. The system of claim 20wherein the weighted electrical dyssynchrony includes a weighting factorassociated with each of the electrodes of the left ventricularelectrodes, each weighting factor based on each electrode's distancefrom the pacing electrode.
 22. The system of claim 21 furthercomprising: means for averaging activation times associated with thefirst one when two or more of the left ventricular electrodes aresubstantially close; and means for averaging activation times associatedwith the second one when two or more of the left ventricular electrodesare substantially close.
 23. The system claim 22, wherein substantiallyclose is within about 1.5 mm.
 24. The system of claim 20 furthercomprising: means for determining that the optimal A-V delay isassociated with a lowest value of weighted electrical dyssynchrony. 25.The system of claim 20 further comprising: means for determining thatthe optimal A-V delay is associated with a smallest value A-V delay ifthe first and second A-V delays are associated with equal values ofelectrical dyssynchrony.
 26. The system of claim 25 further comprising:means for determining a weighted electrical dyssynchrony for N number ofA-V delays; and means for comparing weighted electrical dyssynchrony forthe N A-V delays, wherein N is any number between 2 and
 100. 27. Thesystem of claim 26 wherein the optimal A-V delay is a last remaining A-Vdelay that has not been eliminated out of N A-V delays.
 28. The systemof claim 27 wherein the optimal sensed A-V delay is determined bysubtracting ΔAV_(rest) from the optimal paced A-V delay.
 29. The systemof claim 26 determining an optimal sensed A-V delay for eachcorresponding atrial rate.
 30. The system of claim 26 wherein N numberranges from 2 to about
 100. 31. The system of claim 26 wherein a look-uptable of optimal paced and sensed A-V delays for different atrial ratesmay be stored and paced and sensed A-V delays are adapted accordingly inresponse to changes in the atrial rates during subsequent delivery ofcardiac resynchronization therapy.
 32. The system of claim 25 whereinthe optimal paced A-V delay is determined for each of N number of atrialpacing rates above the resting atrial rate but less than or equal to aprogrammed atrial upper tracking rate.
 33. The system of claim 20further comprising: means for eliminating either the first or the secondA-V delays whichever A-V delay is associated with a greater value ofelectrical dyssynchrony.
 34. The system of claim 20 further comprising:means for eliminating either the first A-V delay or the second A-V delaybased upon whichever A-V delay has a greater value when the weightedelectrical dyssynchrony for the first and the second A-V delays areequal.
 35. The system of 20 wherein the first and second A-V delay areassociated with atrial sense at a resting atrial rate.
 36. The system ofclaim 35 wherein the resting atrial rate is between about 50 to about 75beats per minute.
 37. The system of claim 35 wherein the first andsecond A-V delay are associated with atrial pacing performed at a rategreater than or equal to a resting atrial rate and less than or equal toa programmed atrial upper tracking rate.
 38. The system of claim 37wherein determining ΔAV_(rest) by subtracting an optimal sensed A-Vdelay from an optimal paced A-V delay.
 39. A method of cardiac pacingemploying a right ventricular electrode and a plurality of leftventricular electrodes, comprising: a) pacing using the rightventricular electrode and a pacing left ventricular electrode using afirst A-V delay; b) measuring activation times at other ones of the leftventricular electrodes in response to pacing the right ventricularelectrode and a pacing left ventricular electrode; c) determining aweighted electrical dyssynchrony associated with the first A-V delay; d)pacing using the right ventricular electrode and the pacing leftventricular electrodes using a second A-V delay; e) measuring activationtimes at other ones of the left ventricular electrodes the rightventricular electrode and a pacing left ventricular electrode; and f)determining a weighted electrical dyssynchrony for the second A-V delay;g) comparing weighted electrical dyssynchrony for the first and thesecond A-V delays; h) selecting an optimal A-V delay in response tocomparing weighted electrical dyssynchrony for the first and the secondA-V delays, wherein the weighted electrical dyssynchrony includes aweighting factor associated with each of the electrodes of the leftventricular electrodes, each weighting factor based on each electrode'sdistance from the pacing electrode, wherein the weighted electricaldyssynchrony is determined using${{ED}\left( {I,A,D} \right)} = {\sum\limits_{i = 1}^{n}{{w\left( {1,I} \right)}{{AT}\left( {1,A,D} \right)}}}$ wherein factor w(i, j) is a distance of a sensing electrode I from apacing electrode, n is a total number of left ventricular electrodes,atrio-ventricular delay, and D is a time delay between pacing pulses ina right ventricle and a left ventricle.
 40. The method of claim 39further comprising: averaging activation times associated with the firstone when two or more of the left ventricular electrodes aresubstantially close; and averaging activation times associated with thesecond one when two or more of the left ventricular electrodes aresubstantially close.
 41. The method of claim 40 where substantiallyclose being within 1.5 mm.